O6-methylguanine-DNA methyltransferase activity in the human lung persists with advancing age.

Abstract

O6-methylguanine-DNA methyltransferase (MGMT) plays an important role in the repair of DNA lesions induced by alkylating carcinogens in a wide range of animals. To determine the relationship between DNA repair activity and tumor susceptibility with advancing age the activity of MGMT was measured in normal lung tissue extracts from 66 patients with primary or metastatic lung cancer obtained at surgery. The age of the patients whose lung MGMT activity was measured ranged from 40 to 79 years (males) and from 40 to 80 years (females), and the values varied over 10-fold in both sexes (33 males and 33 females). Our results indicate that the MGMT enzyme protein is expressed at appreciable levels throughout life, and on age-associated rapid decline is not a feature in the human lung. Thus, any age-associated increase in lung cancer incidence cannot be ascribed to any change in MGMT activity. In order to assess other possible factors which might exert a modulating influence we examined the MGMT activity in relation to sex, tumor type and smoking. However, in none of these cases was any significant correlation evident.